Fourier Transform Mass spectrometry (FTMS) can be used in Life Sciences for analysis of peptides, proteins and other heavy biological molecules. However, specific problems arise in FTMS in the analysis of heavy protein ions. These problems may also arise with other heavy biological molecule ions but protein ions will be referred to herein for illustration. Accordingly, the invention is not limited in application to analysis of proteins. A wide isotopic distribution of heavy protein ions results in a unique interference effect observed in FTMS. Initial constructive interference between the ion oscillations is quickly followed by destructive interference, when practically no signal is detected from those ions. This effect is discussed in Hofstadler et al, “Isotopic Beat Patterns in Fourier Transform Ion Cyclotron Resonance Mass Spectrometry: Implications for High Resolution Mass Measurements of Large Biopolymers”, Int. J. Mass Spectrom. Ion Proc. 1994, 132, 109-127. and A. A. Makarov, E. Denisov. “Dynamics of ions of intact proteins in the Orbitrap mass analyzer”, J. Am. Soc. Mass Spectrom. 2009, 20, 1486-1495.
As a result, the detected transient signal for such ions comprises a characteristic beat pattern, identifiable in the frequency domain. For heavier proteins, multiple beats are spaced further apart from one another in frequency. However, rapid signal decay in time is caused by collisions with residual gas and sometimes metastable fragmentation. In view of this, the second beat is frequently not observed for many heavier proteins of pharmaceutical importance (such as antibodies with molecular weight around 150 kDa).
In many cases, the first beat alone is sufficient to separate isotopic distributions corresponding to different modifications, such as glycosylation. However, the intensity of this beat in FTMS is at highest immediately after excitation of the ions. In other words, this is at the very first few milliseconds of the transient. It is difficult to obtain a transient signal suitable for detection of ions this quickly following excitation.
This difficulty is especially aggravated in orbital trapping Fourier Transform mass spectrometry, for example using an Orbitrap (trade mark) mass spectrometer where excitation is done by an injection process involving applying voltages on a deflector electrode and the central electrode of the trap. Subsequent settling time of voltages on the deflector electrode and the central electrode (providing a substantially electrostatic field during detection) could extend up to 20 ms. Reducing this settling time is desirable to address this issue. Similar problems exists in other forms of electrostatic traps.